Nova is a family of highly conserved, nuclear RNA-binding proteins that is a target antigen in subcortical motor degeneration associated with breast and lung cancer. X-ray crystallographic studies are being undertaken to determine a high-resolution structure of the various domains of the Nova-1 protein. MALDI-MS has been employed for domain elucidation to assist in designing well-behaved constructs for crystallization trials. ESI- and MALDI-MS are also being used to monitor the incorporation of heavy atoms into the protein constructs for phase determination.